Dynamics of Donor-Derived Cell-Free DNA at the Early Phase After Pediatric Kidney Transplantation: A Prospective Cohort Study

Abstract

Background: Donor-derived cell-free DNA (ddcfDNA) has been suggested as an indicator of allograft injury in adult and pediatric kidney transplantation (KTx). However, the dynamics of ddcfDNA in pediatric KTx have not been investigated. In addition, it has not been demonstrated whether donor-recipient (D/R) size mismatch affect ddcfDNA level.Methods: Pediatric KTx recipients with a single donor kidney were enrolled and followed up for 1 year. ddcfDNA, calculated as a fraction (%) in the recipient plasma, was examined longitudinally within 3 months post-transplant. D/R size mismatch degree was described as D/R height ratio. The 33rd percentile of D/R height ratio (0.70) was used as the cut-off to divide the patients into low donor-recipient height ratio group (<0.70) and high donor-recipient height ratio group (≥0.70). The dynamics of ddcfDNA were analyzed and the impact factors were explored. Stable ddcfDNA was defined as the first lowest ddcfDNA. ddcfDNA flare-up was defined as a remarkable elevation by a proportion of >30% from stable value with a peak value >1% during elevation.Results: Twenty-one clinically stable recipients were enrolled. The median D/R height ratio was 0.83 (0.62–0.88). It took a median of 8 days for ddcfDNA to drop from day 1 and reach a stable value of 0.67% (0.46–0.73%). Nevertheless, 61.5% patients presented ddcfDNA>1% at day 30. Besides, 81.0% (17/21) of patients experienced elevated ddcfDNA and 47.6% (10/21) met the standard of ddcfDNA flare-up. Donor-recipient height ratio was an independent risk factor for ddcfDNA flare-up (odds ratio = 0.469 per 0.1, 95% CI 0.237–0.925, p = 0.029) and low donor-recipient height ratio (<0.70) was found to increase the risk of flare-up occurrence (odds ratio = 15.00, 95% CI 1.342–167.638, p = 0.028).Conclusions: ddcfDNA rebounds in many stable pediatric KTx recipients without rejection. This may be induced by significant D/R size mismatch and may affect its diagnostic performance at the early phase after pediatric KTx in children.

Longitudinal Evaluation of Donor-Derived Cellfree DNA in Pediatric Kidney Transplantation

“…Our results are consistent with the only other published pediatric study. Nie et al (26) showed that median donor-derived cfDNA at day 30 post-transplant was 0.90%; at day 60, it was 0.64% (0.47%-0.87%), and at day 90, it was 0.63%. However, this study did not evaluate the donor-derived cfDNA levels out to 1-year post-transplant as we did, nor did they stratify out the younger recipients.…”

Single center study investigating the clinical association of donor-derived cell-free DNA with acute outcomes in lung transplantation

“…While we observed the %dd-cfDNA reached the baseline level within 2 weeks and decreased at 86.5% from the peak value in this study, the trend of %dd-cfDNA could differ among the organ types. Studies in kidney transplant demonstrated that %dd-cfDNA converged to the plateau within a week ( 19 – 21 ), while the multicenter study “GRAfT” for heart transplants showed it reached the baseline by ∼60 days ( 22 ). Allograft cell death should correlate with grade of ischemia-reperfusion injury and PGD after solid organ transplantation ( 23 ).…”

Immune monitoring in pediatric kidney transplant

“…Dandamudi et al 61 reported that pediatric recipients with a donor-to-recipient body surface area (BSA) ratio >1.5 took 8 months after transplantation for dd-cfDNA level to reach its baseline of 0.23%, whereas patients with a BSA ratio ≤1.5 reached dd-cfDNA nadir of 0.14% after 4 months post-transplant. Nie et al 62 reported that more than 60% of pediatric transplant recipients had dd-cfDNA over 1.0% at 1 month after transplant and this proportion decreased to 20.0% and 11.1% at 2 and 3 months, respectively. Thus, the 1.0% cut-off may lead to a high rate of false-positive in children early post-transplant.…”